Dermacoccus abyssi sp. nov. strains MT1.1 and MT1.2 are actinomycetes isolated from a Mariana Trench sediment at a depth of 10 898 m. The fermentation process using complex media led to the production of three new pigmented heteroaromatic (oxidized and reduced) phenazine compounds, dermacozines H−J (1−3). Extensive use was made of 1D and 2D NMR experiments and high-resolution MS to determine the structures of the compounds. The new dermacozines showed radical scavenging activity, and the highest activity was observed for dermacozine H (1), with an IC50 value of 18.8 μM.

Molecular modelling studies were performed on some previously reported novel quinoxaline-2-carboxamide 1,4-di-N-oxide derivatives (series 1–9). Using the LigandScout program, a pharmacophore model was developed to further optimize the antimycobacterial activity of this series of compounds. Using the Dock6 program, docking studies were performed in order to investigate the mode of binding of these compounds. The molecular modeling study allowed us to confirm the preferential binding mode of these quinoxaline-2-carboxamide 1,4-di-N-oxide derivatives inside the active site. The obtained binding mode was as same as that of the novobiocin X-ray structure.

Molecular modelling studies were performed on some previously reported novel quinoxaline-2-carboxamide 1,4-di-N-oxide derivatives (series 1–9). Using the LigandScout program, a pharmacophore model was developed to further optimize the antimycobacterial activity of this series of compounds. Using the Dock6 program, docking studies were performed in order to investigate the mode of binding of these compounds. The molecular modeling study allowed us to confirm the preferential binding mode of these quinoxaline-2-carboxamide 1,4-di-N-oxide derivatives inside the active site. The obtained binding mode was as same as that of the novobiocin X-ray structure.

As part of a search for antitubercular substances from natural sources, we screened a library of endophytic microbes (50 strains and 300 crude extracts in total) isolated from traditional Chinese medicines (TCMs) for growth inhibitory activity against Bacillus Calmette-Guérin (BCG). The crude extract of Streptomyces sp. strain Y3111, which was associated with the stems of Heracleum souliei, showed good anti-BCG activity with an MIC value of 12.5 μg/mL. Bioassay-guided isolation led to four new pluramycin-type compounds, heraclemycins A–D (1–4). Their structures were determined by different spectroscopic techniques including HRMSESI, 1D NMR, and 2D NMR. This is the first report of pluramycin analogues produced by TCM endophytic microbes as well as the first example of BCG-selective pluramycins. Heraclemycin C (3) showed selective antitubercular activity against BCG with a MIC value of 6.25 μg/mL and a potential new mode of action.

A versatile methodology to develop an inherently fluorescent and thus traceable multifunctional nanodelivery platform based on miktoarm polymers is reported. Miktoarm stars containing covalently linked tetraiodofluorescein dye, polyethylene glycol, and polycaprolactone self-assemble into micelles, and integrate multiple functions including fluorescent tags for imaging, a hydrophobic core for drug incorporation, and a hydrophilic corona for micelle stabilization. Curcumin, a pleiotropic but very poorly water-soluble drug, is loaded into these micelles with an efficiency of 25–60 wt%. It leads to a 25 000-fold increase in its aqueous solubility, and a sustained release over a period of 7 d. These micelles are rapidly internalized into murine J774A.1 macrophages, and accumulated into discrete cellular compartments, whereas the free and physically encapsulated dye is diffused in the cytoplasm. Curcumin-loaded micelles reduce lipopolysaccharide-induced nitric oxide release. The studies establish miktoarm star based nanocarriers as highly efficient in tracking their fate and expanding the scope of pharmacological agents with limited utility in experimental medicine.

Sertaconazole nitrate is a broad spectrum imidazole antifungal agent with antibacterial and anti-inflammatory properties. However, its lipophilic nature and very poor aqueous solubility limit its use in the clinic. The aim of this study was to develop and characterize poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-b-PCL) polymeric nanomicelles for the solubilization and enhancement of sertaconazole antifungal activity. Sertaconazolewas incorporated into PEG-b- PCL polymeric nanomicelles by a co-solvent evaporation method and micelle size, drug loading capacity and drug release properties were determined. The antifungal properties of nanomicelle-loaded drug were evaluated in Fusariummiscanthi, Microsporumcanis, and Trichophytonmentagrophytes isolated, respectively from fungal keratitis, ringworm, and tineacorporis. PEG-b-PCL formed nanomicelles in aqueous solution with a diameter ranging from 40-80 nm, depending on the polymer composition and level of drug loading. Drug loading properties of the nanomicelles were dependent on the PCL block molecular weight and drug/polymer weight feed ratio. Drug encapsulation efficiency of up to 85% was achieved and this resulted in more than 80-fold enhancement in sertaconazole aqueous solubility at polymer concentration of 0.2%. Drug release studies showed an initial burst release followed by sustained drug release for 72 hours. In vitro antimycotic studies showed that nanomicelle-incorporated sertaconazole inhibited fungal growth in a concentration dependent manner. Further, it was more effective than the free drug in inhibiting the growth of Fusariummiscanthi and Microsporumcanis. These results confirm the utility of PEG-b-PCL nanomicelles in enhancing the aqueous solubility and antifungal activity of sertaconazole or other similar antifungal drugs.

Sertaconazole nitrate is a broad spectrum imidazole antifungal agent with antibacterial and anti-inflammatory properties. However, its lipophilic nature and very poor aqueous solubility limit its use in the clinic. The aim of this study was to develop and characterize poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-b-PCL) polymeric nanomicelles for the solubilization and enhancement of sertaconazole antifungal activity. Sertaconazolewas incorporated into PEG-b- PCL polymeric nanomicelles by a co-solvent evaporation method and micelle size, drug loading capacity and drug release properties were determined. The antifungal properties of nanomicelle-loaded drug were evaluated in Fusariummiscanthi, Microsporumcanis, and Trichophytonmentagrophytes isolated, respectively from fungal keratitis, ringworm, and tineacorporis. PEG-b-PCL formed nanomicelles in aqueous solution with a diameter ranging from 40-80 nm, depending on the polymer composition and level of drug loading. Drug loading properties of the nanomicelles were dependent on the PCL block molecular weight and drug/polymer weight feed ratio. Drug encapsulation efficiency of up to 85% was achieved and this resulted in more than 80-fold enhancement in sertaconazole aqueous solubility at polymer concentration of 0.2%. Drug release studies showed an initial burst release followed by sustained drug release for 72 hours. In vitro antimycotic studies showed that nanomicelle-incorporated sertaconazole inhibited fungal growth in a concentration dependent manner. Further, it was more effective than the free drug in inhibiting the growth of Fusariummiscanthi and Microsporumcanis. These results confirm the utility of PEG-b-PCL nanomicelles in enhancing the aqueous solubility and antifungal activity of sertaconazole or other similar antifungal drugs.

Sertaconazole nitrate is a broad spectrum imidazole antifungal agent with antibacterial and anti-inflammatory properties. However, its lipophilic nature and very poor aqueous solubility limit its use in the clinic. The aim of this study was to develop and characterize poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-b-PCL) polymeric nanomicelles for the solubilization and enhancement of sertaconazole antifungal activity. Sertaconazolewas incorporated into PEG-b- PCL polymeric nanomicelles by a co-solvent evaporation method and micelle size, drug loading capacity and drug release properties were determined. The antifungal properties of nanomicelle-loaded drug were evaluated in Fusariummiscanthi, Microsporumcanis, and Trichophytonmentagrophytes isolated, respectively from fungal keratitis, ringworm, and tineacorporis. PEG-b-PCL formed nanomicelles in aqueous solution with a diameter ranging from 40-80 nm, depending on the polymer composition and level of drug loading. Drug loading properties of the nanomicelles were dependent on the PCL block molecular weight and drug/polymer weight feed ratio. Drug encapsulation efficiency of up to 85% was achieved and this resulted in more than 80-fold enhancement in sertaconazole aqueous solubility at polymer concentration of 0.2%. Drug release studies showed an initial burst release followed by sustained drug release for 72 hours. In vitro antimycotic studies showed that nanomicelle-incorporated sertaconazole inhibited fungal growth in a concentration dependent manner. Further, it was more effective than the free drug in inhibiting the growth of Fusariummiscanthi and Microsporumcanis. These results confirm the utility of PEG-b-PCL nanomicelles in enhancing the aqueous solubility and antifungal activity of sertaconazole or other similar antifungal drugs.

Objective: The development of injectable and stable hydrogels for protein delivery is a major challenge. Therefore, the objective of this study was to evaluate the potential of polymerized β-CD for the formulation of stable hydrogels suitable for loading and release of bioactive agents and to investigate the mechanism of hydrogel formation. Methods: Hydrogels based on the inclusion complexation of polymerized β-cyclodextrin and cholesterol terminated poly(ethylene glycol) polymers were formed by rehydration of a lyophilized mixture of both polymers. The mechanism of hydrogel formation was investigated via isothermal titration calorimetry, fluorescence spectroscopy and dynamic light scattering measurements. The release behavior of bovine serum albumin (BSA) as a model protein from the modified gels was explored. Results: Rheological analysis demonstrated that the prepared hydrogels had a viscoelastic behavior even at elevated temperature (> 37°C). There are two competing mechanisms for hydrogel formation. The first mechanism is the inclusion complexation between cholesterol moieties and β-CD cavities. The second one is the self association of cholesterol modified PEGs. β-CD had the ability to dissociate the PEG-cholesterol associations. The quantitative and complete release of BSA was observed within 4 weeks. Conclusion: The polymerized form of β-CD, rather than native β-CD is essential for the formation of stable hydrogels. These results were supported by the ability of the modified hydrogel system for loading and release of BSA, making such hydrogel systems promising devices in drug delivery applications.

Catechol-containing molecules, such as hydrocaffeic acid (HCA) have been shown to increase the mucoadhesion of several polymers. We report here a simple and bioinspired approach to enhance chitosan (CS) mucoadhesion and stabilize it in nanoparticulate form by preparing HCA–CS conjugates. HCA–CS conjugates containing 6 and 15 mol% HCA were synthesized and characterized by FT-IR, 1H NMR and UV–vis spectrophotometry. HCA–CS nanoparticles prepared by ionic gelation with sodium tripolyphosphate (TPP) ranged in size between 100 and 250 nm depending on the polymer and TPP/CS weight ratio. In contrast to CS nanoparticles, which aggregate at pH > 6.5, HCA–CS nanoparticles did not show any sign of aggregation or precipitation over the 4–10 pH range and maintain their size. Unexpectedly, HCA–CS nanoparticles also maintained their size and polydispersity index at pH 7.4 and NaCl concentrations of up to 500 mM. Partial oxidation of HCA resulted in nanoparticle cross-linking and improved stability at pH 4. HCA–CS mucoadhesion to rabbit small intestine was 6 times higher than unmodified CS. CS and HCA–CS nanoparticles were able to induce reversible tight junction opening in Caco-2 cell monolayers. Tight junction opening facilitated the permeability of a model hydrophilic molecule, fluorescein isothiocyanate-labeled dextran (FD4) and was 3 times higher in the cells treated with HCA–CS 15% nanoparticles compared to control groups. HCA–CS conjugates were found to be excellent candidates for stable nanodelivery systems with enhanced oral absorption of hydrophilic molecules.